Recent technological advances in our ability to study the coronary microcirculation both in vivo and in vitro have opened a new vista of research related to regulation of the coronary microcirculation. Observations from our laboratory indicate that about one-half of coronary vascular resistance exists in arterial vessels larger than 100 mu m in size and that the distribution of coronary microvascular resistance is dramatically altered in the presence of coronary occlusion or a severe coronary obstruction. The purpose of the proposed studies will be to perform further investigations aimed at understanding mechanisms that regulate the coronary circulation both under control conditions and during myocardial ischemia. Major subaims are related to: effects of exogenously applied and endogenously released substances (thromboxane, PGI2, leukotrienes, norepinephrine, adenosine and serotonin) on the distribution of coronary microvascular resistance; studies of regional alterations in permeability in the coronary microcirculation following reperfusion; distribution of receptors in various class sizes of arterial microvessels; and, effects of nitroglycerine and nifedipine on the distribution of coronary microvascular resistance. Completion of these investigations should significantly augment our basic understanding of mechanisms that regulate myocardial perfusion under control conditions and in various models of myocardial ischemia.